Intracranial venous thrombosis after hypoxic-ischemic brain insult in two newborns: could low serum carnitine levels have contributed?

Sinovenous thrombosis is a definite cause of mortality or morbidity in newborns. Perinatal hypoxia is one of the well known risk factors. Two term newborns were diagnosed to have cerebral venous thrombosis after a hypoxic-ischemic insult. They were later found to have carnitine deficiency. Both of the patients died. Carnitine was previously shown to have inhibitory effects on thrombogenesis in experimental studies. The possible contribution of carnitine in thrombogenesis was discussed.     

Sigma receptors and cancer: possible involvement of ion channels

The sigma (sigma) receptor and its agonists have been implicated in a myriad of cellular functions, biological processes and diseases. Whereas the precise molecular mechanism(s) of sigma receptors and their involvement in cancer cell biology have not been elucidated, recent work has started to shed some light on these issues. A molecular model has been proposed for the cloned sigma1 receptor; the precise molecular nature of the sigma2 receptor remains unknown. sigma receptors have been found to be frequently up-regulated in human cancer cells and tissues. sigma2 receptor drugs particularly have been shown to have antiproliferative effects. An interesting possibility is that sigma and/or sigma1 drugs could produce anticancerous effects by modulating ion channels. As well as proliferation, a variety of other metastatic cellular behaviors such as adhesion, motility, and secretion may also be affected. Other mechanisms of sigma receptor action may involve interaction with ankyrin and modulation of intracellular Ca(2+) and sphingolipid levels. Although more research is needed to further define the molecular physiology of sigma receptors, their involvement in the cellular pathophysiology of cancer raises the possibility that sigma drugs could be useful as novel therapeutic agents.     

Aberrant expression of insulin-like growth factor-2 (IGF-2) in Philadelphia chromosome negative chronic myeloproliferative disorders

Philadelphia chromosome negative chronic myeloproliferative disorders (Ph- CMPD) comprise haematopoietic stem cell disorders with currently unknown underlying molecular defect. Insulin-like growth factor 2 (IGF-2) is an imprinted gene that is known to be involved in the regulation of normal cell growth and that is overexpressed by a variety of tumors. The expression of IGF-2 in bone marrow cells is largely unknown. In order to elucidate gene expression level, protein expression pattern, and a potential role of IGF-2 in the pathogenesis of Ph- CMPD, we quantitatively analyzed the expression of the IGF-2 gene in bone marrow cells of 69 cases with Ph- CMPD and 31 control cases by applying real-time RT-PCR. IGF-2 gene expression in idiopathic myelofibrosis (IMF) was significantly increased by up to 11-fold as compared to the control group (P < 0.0001). IMF also expressed higher IGF-2 gene level as compared to essential thrombocythaemia (ET) and polycythaemia vera (PV) (P < 0.0001, P = 0.005, respectively). Paranuclear IGF-2 protein could be demonstrated in IMF, ET, and PV exclusively in megakaryocytes and myeloid progenitor cells in contrast to undetectable IGF-2 protein in control cases. We conclude that overexpression of the IGF-2 gene is a pathogenic feature in IMF. In addition, an abundant translational and post-translational processing could explain the accumulation of IGF-2 protein detectable in all Ph- CMPD entities in contrast to non-neoplastic haematopoiesis. We conclude that IGF-2 represents a new molecular target for evaluation of underlying fundamental pathomechanisms in Ph- CMPD.     

Prolonged hyperglycemia in the early subacute period after cerebral infarction: effects on short term prognosis

Although the adverse effect of admission hyperglycemia in cerebral infarction on prognosis is well known, studies generally have not questioned the effect of hyperglycemia in the early subacute period on prognosis after a stroke. Forty-six patients with acute ischemic stroke were seperated into 3 groups: Group 1) Known diabetes or admission blood glucose (ABG) > or = 140 mg/dl and HbA1c > or = 8,0%); Group 2) ABG > or = 140 mg/dl and HbA1c < 8,0%; and Group 3) ABG < 140 mg/dl and HbA1c < 8,0%. Blood glucose was followed-up 4 times a day for 10 days after the stroke and the mean of these measurements was calculated as the mean of glycemic regulation (MGR). Neurological evaluation was done at presentation and on day 10 and 30 with the National Institute of Health (NIH) scale. Oedema, lesion size and presence of hemorrhagic transformation were evaluated using CT. The MGR was significantly higher in group 1 compared to the other two groups (p < 0,001 and p < 0,01) and in group 2 compared to group 3 (p < 0,001). Patients with clinical worsening had a significantly higher MGR (p < 0,05). Patients with marked cerebral edema had a significantly higher MGR (p < 0,01) compared to patients with lesser edema. No correlation was found between MGR and lesion size or hemorrhagic transformation. Our results show that hyperglycemia in the early subacute period after cerebral infarction is associated with more pronounced cerebral edema and has an adverse effect on short term prognosis. We suggest that studies investigating the effect of insulin infusion on stroke prognosis should also consider infusions for a longer period than 24 hours.     

Byler's disease and anesthetic consideration

Byler's disease is an autosomal recessive condition characterized by intrahepatic cholestasis, progressive fibrotic changes and finally cirrhosis that leads to death during childhood. This is a report of a six-year-old girl with Byler's disease and retrobulbar hematoma as a result of trauma who underwent enucleation and implantation. This case report describes the anesthetic features of a patient with Byler's disease in which anesthetic agents with no or minimal hepatotoxic effect should be used to avoid deterioration of liver function.     

The effects of estrogen and raloxifene treatment on antioxidant enzymes in brain and liver of ovarectomized female rats

Recent studies documented that estrogen have antioxidant properties in-vitro, there are conflicting results on the effect of estrogen in vivo. We aimed to investigate the effects of estradiol and Raloxifene on the antioxidant enzyme [superoxide dismutase (SOD) and catalase (CAT)] activities and MDA levels in brain and liver homogenates of ovariectomized female rats. Twelve weeks after ovariectomy, female Sprague-Dawley rats (n = 26) were divided into three groups: (1) Ovariectomized placebo group (n = 6) was given physiologic saline. (2) Estrogen group (n = 10) was given Ethynyl estradiol, 0.1 mg/kg sc. (3) Raloxifene group (n = 10) was given raloxifene, 1 mg/kg sc during 8 weeks. Ten rats were used as naive controls without any treatment (Sham operated group, n = 10). Ovariectomy lead to an increase in the CAT activities in liver tissue samples compared to the sham group (p = 0.056, Mann-Whitney test). While estrogen treatment reversed to normal levels of CAT activities, raloxifene remained as ineffective. Superoxide dismutase activities and MDA levels in liver were remained unchanged in all groups. There was no significant change in the brain tissue SOD and CAT activities between the control ovariectomy, estrogen treated, and raloxifen treated groups. We determined an increase in MDA levels in brain of ovariectmised rat (p = 0.02). While raloxifene treatment reversed to normal levels of MDA (p = estrogen treatment failed. Our data showed that estrogen may play a role in regulation of CAT and SOD activities in liver due to its antioxidative effects. We can suggest estrogen and raloxifene exert their antioxidative effects in brain rather than liver. Since Raloxifene's effect is more clear than estradiol, raloxifene may be suggested primarily for treatment and/or prevention of diseases which can be resulted from oxidative stress in postmenopausal women.     

Effects of extended-wear soft contact lenses on the ocular surface and central corneal thickness

PURPOSE: New contact lens materials with high oxygen permeability are said to be convenient for the extended-wear (EW) schedule. We evaluated the short-term effect of EW soft contact lens usage on ocular surface and central corneal thickness. PATIENTS AND METHODS: Fifty-two eyes of 26 patients were included in the study. Sixteen of the patients used the high oxygen-permeable lenses for a 30-day extended-wear schedule (group I). Ten patients used the lenses on a daily wear basis (DW, group II). All patients were evaluated for visual acuity and central corneal thickness by corneal and conjunctival biomicroscopy, Schirmer and tear break-up time (BUT) tests. Impression cytology was performed in the superior/temporal, inferior/nasal quadrants of the conjunctiva, 1 mm from the limbus, with cellulose acetate filter paper. The specimens were graded under light microscopy according to Nelson's classification. RESULTS: Three patients in the EW group were excluded from the study as they discontinued lens usage due to slight discomfort and hyperemia. Biomicroscopic findings and tear function tests indicated no increased pathological results. Central corneal thickness decreased from 554 +/- 9.55 to 546 +/- 9.30 microm (mean +/- SEM) in the EW group (p = 0.002), whereas no significant change occurred in the DW group. Cytological evaluation of the EW group showed an 88% increase in metaplasia (p = 0.007), especially close to the limbal areas and in the superior quadrants; this ratio was 30% in the DW group. Snake-like chromatin changes were found to be increased, from 4 to 6 patients, in the EW group while it remained the same in the DW group (p > 0.05). Individual comparisons of the initial and final pathological conditions of the ocular surfaces in the two groups showed that there was an increase in pathology in the EW group while there was no significant difference in the DW group. CONCLUSIONS: On a 30-day extended-wear basis with high oxygen-permeable lenses, the possible development and increase of conjunctival cytologic changes secondary to mechanical trauma is one of the main remaining problems. Conjunctival and related immunologic pathologies should not be overlooked when prescribing an extended-wear lens schedule.     

The influence of sex hormones on ocular blood flow in women

PURPOSE: To investigate the influence of sex hormones on ocular haemodynamics, blood flow velocities in the ophthalmic and central retinal arteries and serum levels of sex hormones were measured in pre- and postmenopausal women. METHODS: Colour Doppler imaging (CDI) was used to determine the flow velocities (peak systolic velocity [PSV] and end-diastolic velocity [EDV]) and the resistive index (RI) in the ophthalmic and central retinal arteries in 22 premenopausal and 32 postmenopausal women, who had never received hormone replacement therapy. Serum levels were measured for oestradiol, free testosterone and follicle-stimulating hormone. The CDI parameters were compared between the two groups and the influence of serum levels of oestradiol and testosterone on blood flow velocities and the resistive indices were analysed. RESULTS: After correcting for age and mean arterial blood pressure, an analysis of covariance disclosed a significantly lower EDV (p=0.02) and a significantly higher RI (p=0.01) in the central retinal artery of postmenopausal women compared with premenopausal women. Partial correlation analysis, controlling for age, revealed significant correlations between the CDI parameters and serum levels of oestradiol and testosterone. For premenopausal women, PSV (r=0.58, p=0.04) and EDV (r=0.73, p=0.006) in the ophthalmic artery correlated positively with serum oestradiol levels. The RI in the central retinal artery decreased with increasing oestradiol levels in both groups (premenopausal r= -0.40, p=0.04; postmenopausal r= -0.32, p=0.05). Peak systolic velocity in the central retinal artery correlated negatively (r= -0.49, p=0.04), whereas the RI correlated positively (r=0.53, p=0.02) with testosterone levels in the premenopausal group. Postmenopausal women with higher testosterone levels had lower EDV (r= -0.53, p=0.007) in the central retinal artery and higher RI in both vessels (ophthalmic artery r=0.48, p=0.01; central retinal artery r=0.61, p=0.002). CONCLUSION: Our data provide evidence of a relationship between serum sex hormone levels and blood flow velocities and resistive indices in retrobulbar arteries. Oestradiol appears to have beneficial effects on ocular haemodynamics, whereas testosterone may act as an antagonistic to the effects of oestrogen.     

Comparison of fentanyl-bupivacaine or midazolam-bupivacaine mixtures with plain bupivacaine for caudal anaesthesia in children

BACKGROUND: The aim of this study was to evaluate the intensity and effectiveness of 0.75 ml.kg-1 bupivacaine 0.25% with the addition of fentanyl or midazolam for caudal block in children undergoing inguinal herniorrhaphy. METHODS: Seventy-five children were allocated randomly to three groups to receive a caudal block with either 0.25% bupivacaine with fentanyl 1 microg.kg(-1) (group BF) or with midazolam 50 microg.kg(-1) (group BM) or bupivacaine alone (group B) after induction of anaesthesia. Haemodynamic parameters, degree of pain, additional analgesic requirements and side-effects were evaluated. RESULTS: The mean systolic arterial pressure at 10, 20, 30 min after caudal block was higher in group B compared with groups BF and BM. Mean intraoperative heart rate was lower in group BF than the other groups. Adequate analgesia was obtained in all patients (100%) in group BF, 23 patients (92%) in group BM and 21 patients (84%) in group B (P > 0.05). The time to recovery to an Aldrete score of 10 was significantly shorter in group B than group BM (P < 0.05). Although not significant, it was also shorter in group B than group BF. There was no difference in additional analgesic requirements between the groups in the first 24 h. Sedation score was higher in the midazolam group at 60 and 90 min postoperatively than the other groups. CONCLUSIONS: Caudal block with 0.75 ml.kg(-1) 0.25% bupivacaine and 50 microg.kg(-1) midazolam or 1 microg.kg(-1) fentanyl provides no further analgesic advantages to bupivacaine alone when administered immediately after induction of anaesthesia in children undergoing unilateral inguinal herniorrhaphy.